Rasuvo 12.5mg/0.25ml Pf Inj, 4 Pens
WARNING: Severe side effects like bone marrow problems, liver problems, lung problems, and infections can happen with this drug. Some side effects may not go away and can be deadly. You must talk with the doctor about the risks of this drug. This drug may cause kidney problems in some patients. Talk with the doctor.Regular blood work and other exams will need to be done to check for side effects. Follow what the doctor has told you. Tell your doctor if you have kidney problems or extra fluid around your stomach area or lungs. The chance of side effects may be raised.Talk with your doctor if you are getting radiation. There may be more chance of harm to tissue and bone.New types of cancer have happened in people taking this drug. If you have questions, talk with the doctor.It is common to have diarrhea, upset stomach, throwing up, or mouth sores with this drug. However, sometimes these may be signs of severe and sometimes deadly stomach or bowel problems. Tell your doctor if you get any new or worsening signs. You may need to stop this drug.Severe skin reactions have happened with this drug. These have included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and other severe skin reactions. Sometimes these have been deadly. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin; other skin irritation (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.Very bad and sometimes deadly bone marrow problems and stomach or bowel problems have happened when this drug was taken with nonsteroidal anti-inflammatory drug (NSAIDs) like ibuprofen or naproxen.Not all methotrexate products are used to treat cancer. Talk with the doctor.This drug may cause harm to an unborn baby or loss of an unborn baby. A pregnancy test will be done before you start this drug to show that you are NOT pregnant.If you or your sex partner may become pregnant, you must use birth control while taking this drug and for some time after the last dose. Ask your doctor how long to use birth control. If you or your sex partner gets pregnant, call your doctor right away.Do not take if you are pregnant.This drug must only be used when other drugs cannot be used or have not worked. Talk with your doctor to be sure that the benefits of this drug are more than the risks. @ COMMON USES: It is used to treat some types of arthritis.It is used to treat some types of psoriasis.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antirheumatic, Antineoplastic, Immunosuppressant
Pharmacologic Class
Antimetabolite, Folic acid antagonist
Pregnancy Category
Category X
FDA Approved
Jul 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Rasuvo is a medication that helps reduce inflammation and suppress the immune system. It's used to treat conditions like rheumatoid arthritis, psoriasis, and psoriatic arthritis. It works by interfering with the growth of certain cells in the body, which helps to reduce symptoms of these conditions. It is given as a weekly injection under the skin.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Important Administration Guidelines
Do not inject the medication within 2 inches (5 cm) of the belly button.
Check the solution for cloudiness, leakage, or particles before use. If any of these conditions are present, do not use the medication.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before using another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other items.
When the disposal box is full, follow local regulations for proper disposal.
If you have any questions, consult your doctor or pharmacist.
Dosing and Frequency
Your dosage and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use of this medication can be fatal. Ensure you understand your dosage and administration schedule. If you are unsure, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and the medication's effectiveness.
Handle this medication with care, and consult your doctor or pharmacist for guidance on proper handling.
Additional Recommendations
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store this medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor to determine the best course of action.
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Important Administration Guidelines
Do not inject the medication within 2 inches (5 cm) of the belly button.
Check the solution for cloudiness, leakage, or particles before use. If any of these conditions are present, do not use the medication.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before using another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other items.
When the disposal box is full, follow local regulations for proper disposal.
If you have any questions, consult your doctor or pharmacist.
Dosing and Frequency
Your dosage and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use of this medication can be fatal. Ensure you understand your dosage and administration schedule. If you are unsure, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and the medication's effectiveness.
Handle this medication with care, and consult your doctor or pharmacist for guidance on proper handling.
Additional Recommendations
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store this medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Take exactly as prescribed, usually once a week. Do NOT take daily.
- Avoid alcohol consumption due to increased risk of liver damage.
- Avoid excessive sun exposure and use sunscreen, as methotrexate can cause photosensitivity.
- Maintain good hydration to help with kidney function.
- Discuss all other medications, including over-the-counter drugs, supplements, and herbal remedies, with your doctor or pharmacist.
- Do not receive live vaccines (e.g., MMR, varicella, nasal flu vaccine) while on methotrexate without consulting your doctor.
- Use effective birth control during treatment and for a specified period after (e.g., 6 months for women, 3 months for men) due to severe risks to a fetus.
Available Forms & Alternatives
Available Strengths:
- Rasuvo 10mg/0.2ml Pf Inj, 4 Pens
- Rasuvo 12.5mg/0.25ml Pf Inj, 4 Pens
- Rasuvo 22.5mg/0.45ml Pf Inj, 4 Pens
- Rasuvo 25mg/0.5ml Pf Inj, 4 Pens
- Rasuvo 15mg/0.3ml Pf Inj, 4 Pens
- Rasuvo 17.5mg/0.35ml Pf Inj, 4 Pens
- Rasuvo 20mg/0.4ml Pf Inj, 4 Pens
- Rasuvo 30mg/0.6ml Pf Inj, 4 Pens
- Rasuvo 7.5mg/0.15ml Pf Inj, 4 Pens
- Rasuvo 15mg Inj, 0.3ml
- Rasuvo 17.5mg Inj, 0.35ml
- Rasuvo 20mg Inj, 0.4ml
- Rasuvo 7.5mg Inj, 0.15ml
Dosing & Administration
Adult Dosing
Standard Dose:
7.5 mg to 25 mg once weekly, administered subcutaneously
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
Rheumatoid Arthritis (RA):
Initial: 7.5 mg once weekly. Adjust to achieve optimal response, not to exceed 20 mg once weekly. For Rasuvo, doses up to 25 mg once weekly are indicated.
Psoriasis (PsO) / Psoriatic Arthritis (PsA):
Initial: 10 mg to 25 mg once weekly as a single dose, or 2.5 mg every 12 hours for 3 doses each week (total 7.5 mg). Adjust to achieve optimal response, not to exceed 25 mg once weekly.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly.
Adolescent:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 61-80 mL/min: Use with caution, consider dose reduction.
Moderate:
CrCl 31-60 mL/min: Significant dose reduction (e.g., 50%) or extended dosing interval. Close monitoring required. Some sources suggest avoiding use.
Severe:
CrCl < 30 mL/min: Contraindicated due to risk of severe toxicity.
Dialysis:
Methotrexate is poorly dialyzable by standard hemodialysis. High-flux dialysis or hemoperfusion may be more effective. Contraindicated in patients requiring dialysis due to severe renal impairment.
Hepatic Impairment:
Mild:
Use with extreme caution; monitor liver function closely. Consider dose reduction.
Moderate:
Generally contraindicated due to risk of severe hepatotoxicity.
Severe:
Contraindicated in patients with pre-existing severe liver disease (e.g., cirrhosis, fibrosis, hepatitis).
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that acts as a folic acid antagonist. It competitively inhibits dihydrofolate reductase (DHFR), an enzyme responsible for converting dihydrofolate to tetrahydrofolate. Tetrahydrofolate is essential for DNA synthesis, repair, and cellular replication. By inhibiting DHFR, methotrexate interferes with purine and pyrimidine synthesis, leading to inhibition of DNA and RNA synthesis and cell proliferation. At lower doses used for autoimmune diseases, its mechanism is thought to involve inhibition of T-lymphocyte proliferation, adenosine release, and anti-inflammatory effects.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: Approximately 80-90% (compared to IV). Oral: Variable and dose-dependent (23-90%).
Tmax:
Subcutaneous: 1-2 hours.
FoodEffect:
Not clinically significant for subcutaneous administration. Oral absorption can be delayed by food.
Distribution:
Vd:
0.4-0.8 L/kg (variable, increases with high doses due to saturation of binding sites).
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited at low doses; significant penetration at high doses (e.g., intrathecal administration).
Elimination:
HalfLife:
3-10 hours (low dose); 8-15 hours (high dose, due to slower elimination of polyglutamates).
Clearance:
Primarily renal (glomerular filtration and active tubular secretion).
ExcretionRoute:
Renal (approximately 50-90% unchanged), minor biliary excretion (5-10%).
Unchanged:
50-90%
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: Clinical improvement typically seen within 3-6 weeks, with full effect potentially taking 12 weeks or more.
PeakEffect:
Not directly applicable as a single peak for chronic conditions; refers to maximal therapeutic response over time.
DurationOfAction:
Weekly dosing regimen maintains therapeutic effect.
Safety & Warnings
BLACK BOX WARNING
Methotrexate can cause severe toxic reactions, including death. Patients should be closely monitored for bone marrow, liver, lung, and kidney toxicities. Methotrexate has been associated with severe myelosuppression, hepatotoxicity (fibrosis and cirrhosis), pulmonary toxicity (pneumonitis), and renal toxicity. Diarrhea and ulcerative stomatitis require interruption of therapy. Methotrexate can cause fetal death or teratogenic effects and is contraindicated in pregnant women with non-oncologic diseases. Methotrexate elimination is reduced in patients with impaired renal function, ascites, or significant effusions, leading to increased toxicity. Concomitant use with NSAIDs has been reported to elevate and prolong serum methotrexate levels, resulting in severe toxicity. Malignant lymphomas may occur. Tumor lysis syndrome may occur. Severe skin reactions have been reported. Opportunistic infections, including Pneumocystis jirovecii pneumonia, may occur.
Side Effects
Serious Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding
Signs of pancreatitis (pancreas problem): severe stomach pain, severe back pain, or severe nausea and vomiting
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain
Signs of liver problems: dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes
Signs of lung or breathing problems: shortness of breath, difficulty breathing, cough, or fever
Signs of nerve problems: abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part)
Pinpoint red spots on the skin
Severe dizziness or fainting
Seizures
Confusion
Excessive sleepiness
Changes in vision
Bone pain
Swelling, warmth, numbness, color changes, or pain in a leg or arm
Weakness on one side of the body, speech or thinking difficulties, balance problems, facial drooping, or blurred vision
Headache
Neck stiffness
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have mild ones. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Decreased appetite
Hair loss
Dizziness, fatigue, or weakness
Stomach pain
Common cold symptoms
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding
Signs of pancreatitis (pancreas problem): severe stomach pain, severe back pain, or severe nausea and vomiting
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain
Signs of liver problems: dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes
Signs of lung or breathing problems: shortness of breath, difficulty breathing, cough, or fever
Signs of nerve problems: abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part)
Pinpoint red spots on the skin
Severe dizziness or fainting
Seizures
Confusion
Excessive sleepiness
Changes in vision
Bone pain
Swelling, warmth, numbness, color changes, or pain in a leg or arm
Weakness on one side of the body, speech or thinking difficulties, balance problems, facial drooping, or blurred vision
Headache
Neck stiffness
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have mild ones. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Decreased appetite
Hair loss
Dizziness, fatigue, or weakness
Stomach pain
Common cold symptoms
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of infection: fever, chills, sore throat, body aches, flu-like symptoms.
- Unusual bleeding or bruising: nosebleeds, bleeding gums, red or purple spots under the skin.
- Severe fatigue or weakness.
- Shortness of breath, persistent cough, chest pain.
- Yellowing of skin or eyes (jaundice), dark urine, severe stomach pain, nausea, vomiting.
- Sores in the mouth or throat, severe diarrhea.
- Swelling in the ankles or feet.
- Severe skin rash or blistering.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weak immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult with your doctor to determine the necessary duration for avoiding breast-feeding after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. This will help ensure your safety while taking this medication. Do not initiate, stop, or modify the dose of any medication without first consulting your doctor to confirm that it is safe to do so.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weak immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult with your doctor to determine the necessary duration for avoiding breast-feeding after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. This will help ensure your safety while taking this medication. Do not initiate, stop, or modify the dose of any medication without first consulting your doctor to confirm that it is safe to do so.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
When starting this medication, be cautious and avoid driving or engaging in activities that require alertness until you understand how it affects you. You may be more susceptible to infections, so it is crucial to practice good hygiene by washing your hands frequently and avoiding close contact with individuals who have infections, colds, or flu.
Be aware that this medication may increase your risk of bleeding easily. To minimize this risk, be careful to avoid injuries, use a soft-bristled toothbrush, and consider using an electric razor for shaving.
Before receiving any vaccinations, consult with your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor to understand any potential interactions.
You may be more prone to sunburn while taking this medication, so it is vital to take protective measures. Avoid exposure to direct sunlight, sunlamps, and tanning beds, and use sunscreen with a suitable SPF. Wear protective clothing and eyewear to shield yourself from the sun, and continue these precautions for the duration recommended by your doctor.
If you experience any symptoms of dehydration, such as excessive sweating, vomiting, diarrhea, decreased appetite, or unusual thirst, notify your doctor promptly. This medication can cause severe nervous system problems, which may be temporary or long-lasting and potentially life-threatening. If you have concerns or questions, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor, as this may impact your treatment. Elderly patients (65 years or older) should exercise caution when taking this medication, as they may be more susceptible to side effects.
This medication may affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. It is unclear whether fertility will return to normal if this occurs. If you experience any changes in your menstrual cycle, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
When starting this medication, be cautious and avoid driving or engaging in activities that require alertness until you understand how it affects you. You may be more susceptible to infections, so it is crucial to practice good hygiene by washing your hands frequently and avoiding close contact with individuals who have infections, colds, or flu.
Be aware that this medication may increase your risk of bleeding easily. To minimize this risk, be careful to avoid injuries, use a soft-bristled toothbrush, and consider using an electric razor for shaving.
Before receiving any vaccinations, consult with your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor to understand any potential interactions.
You may be more prone to sunburn while taking this medication, so it is vital to take protective measures. Avoid exposure to direct sunlight, sunlamps, and tanning beds, and use sunscreen with a suitable SPF. Wear protective clothing and eyewear to shield yourself from the sun, and continue these precautions for the duration recommended by your doctor.
If you experience any symptoms of dehydration, such as excessive sweating, vomiting, diarrhea, decreased appetite, or unusual thirst, notify your doctor promptly. This medication can cause severe nervous system problems, which may be temporary or long-lasting and potentially life-threatening. If you have concerns or questions, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor, as this may impact your treatment. Elderly patients (65 years or older) should exercise caution when taking this medication, as they may be more susceptible to side effects.
This medication may affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. It is unclear whether fertility will return to normal if this occurs. If you experience any changes in your menstrual cycle, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe myelosuppression (low white blood cells, red blood cells, platelets)
- Severe mucositis (mouth sores, GI ulcers)
- Severe liver damage
- Kidney failure
- Nausea, vomiting, diarrhea
What to Do:
Seek immediate medical attention. Leucovorin rescue is the primary antidote for methotrexate overdose. Call 1-800-222-1222 (Poison Control Center) or go to the nearest emergency room.
Drug Interactions
Contraindicated Interactions
- Live vaccines (risk of disseminated infection)
- Trimethoprim/sulfamethoxazole (increased myelosuppression)
- Probenecid (decreased renal clearance of methotrexate)
- Salicylates (e.g., aspirin, at high doses; decreased renal clearance)
- Other nephrotoxic drugs (e.g., cisplatin, aminoglycosides, NSAIDs at high doses) - increased methotrexate toxicity
- Other hepatotoxic drugs (e.g., retinoids, azathioprine, sulfasalazine) - increased risk of liver toxicity
- Nitrous oxide (functional folate deficiency, increased myelosuppression)
Major Interactions
- Nonsteroidal Anti-inflammatory Drugs (NSAIDs) (e.g., ibuprofen, naproxen, celecoxib): Increased methotrexate levels and toxicity, especially at higher methotrexate doses or in patients with renal impairment. Use with caution and monitor closely at low-dose methotrexate.
- Proton Pump Inhibitors (PPIs) (e.g., omeprazole, pantoprazole): May increase methotrexate levels, especially at high doses. Monitor for toxicity.
- Phenytoin: Decreased phenytoin levels, increased methotrexate toxicity.
- Sulfonamides (e.g., sulfadiazine): Increased methotrexate toxicity due to displacement from protein binding and/or inhibition of renal tubular secretion.
- Tetracyclines (e.g., doxycycline): May increase methotrexate toxicity.
- Chloramphenicol: May increase methotrexate toxicity.
- Oral antibiotics (e.g., neomycin, ampicillin): May alter gut flora, potentially affecting methotrexate absorption/enterohepatic recirculation.
- Folic acid antagonists (e.g., pyrimethamine): Additive folate deficiency and myelosuppression.
- Theophylline: Methotrexate may decrease theophylline clearance.
Moderate Interactions
- Caffeine: May reduce efficacy of methotrexate in RA/PsO (theoretical, due to adenosine antagonism).
- Leflunomide: Increased risk of hepatotoxicity and myelosuppression.
- Hydroxychloroquine: May increase intracellular methotrexate levels (clinical significance uncertain).
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic parameters and detect pre-existing cytopenias.
Timing: Prior to initiation of therapy
Liver Function Tests (LFTs) including AST, ALT, albumin, bilirubin
Rationale: To assess baseline hepatic function and identify pre-existing liver disease.
Timing: Prior to initiation of therapy
Renal Function Tests (serum creatinine, BUN, estimated GFR)
Rationale: To assess baseline renal function, as methotrexate is primarily renally eliminated.
Timing: Prior to initiation of therapy
Chest X-ray
Rationale: To rule out pre-existing pulmonary disease, as methotrexate can cause pulmonary toxicity.
Timing: Prior to initiation of therapy
Hepatitis B and C serology
Rationale: To screen for viral hepatitis, which can be exacerbated by methotrexate.
Timing: Prior to initiation of therapy
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Weekly for the first month, then every 2-4 weeks for the next 2 months, then monthly or as clinically indicated.
Target: Maintain within normal limits; significant drops (e.g., WBC < 3,500/mm³, platelets < 100,000/mm³) require dose adjustment or discontinuation.
Action Threshold: WBC < 3,500/mm³ or ANC < 1,500/mm³; Platelets < 100,000/mm³; significant drop in hemoglobin.
Liver Function Tests (AST, ALT, albumin)
Frequency: Every 2-4 weeks for the first 2 months, then monthly or as clinically indicated.
Target: Maintain within normal limits; persistent elevation (e.g., AST/ALT > 2-3 times ULN) requires investigation.
Action Threshold: Persistent elevation of AST/ALT > 3 times ULN; significant decrease in albumin.
Renal Function Tests (serum creatinine, BUN)
Frequency: Monthly or as clinically indicated.
Target: Maintain within normal limits; significant increase in creatinine requires dose adjustment.
Action Threshold: Increase in serum creatinine > 50% from baseline or above upper limit of normal.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising (petechiae, purpura)
- Fatigue, weakness, pallor (anemia)
- Shortness of breath, cough, dyspnea (pulmonary toxicity)
- Yellowing of skin or eyes, dark urine, abdominal pain (hepatotoxicity)
- Oral ulcers, stomatitis, severe diarrhea (GI toxicity)
- Skin rash, photosensitivity
Special Patient Groups
Pregnancy
Contraindicated in pregnant women with non-oncologic diseases due to severe risk of fetal death or teratogenic effects (e.g., craniofacial, cardiovascular, and limb abnormalities).
Trimester-Specific Risks:
First Trimester:
Highest risk of major congenital malformations and spontaneous abortion.
Second Trimester:
Risk of fetal toxicity, growth restriction, and potential for abnormalities.
Third Trimester:
Risk of fetal toxicity and complications.
Lactation
Contraindicated during breastfeeding. Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant, including myelosuppression and growth inhibition.
Infant Risk:
High risk (L5 - Contraindicated)
Pediatric Use
Approved for Juvenile Idiopathic Arthritis (JIA) in pediatric patients. Dosing is weight or body surface area-based. Close monitoring for toxicity is essential, similar to adults.
Geriatric Use
Use with caution in elderly patients due to increased likelihood of decreased renal function, which can lead to reduced methotrexate clearance and increased toxicity. Close monitoring of renal function and hematologic parameters is crucial. Consider lower starting doses and slower titration.
Clinical Information
Clinical Pearls
- Methotrexate is a once-weekly medication. Emphasize this to patients to prevent accidental daily dosing, which can be fatal.
- Folic acid supplementation (e.g., 1 mg daily, or 5 mg once weekly, taken on a different day than methotrexate) is often prescribed to reduce common side effects like nausea, oral ulcers, and liver enzyme elevations, without significantly impacting efficacy.
- Patients should be educated on the signs and symptoms of myelosuppression, hepatotoxicity, and pulmonary toxicity, and instructed to report them immediately.
- Avoid alcohol completely while on methotrexate due to the increased risk of liver damage.
- Ensure patients are up-to-date on non-live vaccinations (e.g., flu shot, pneumococcal) before starting methotrexate, as immune response may be blunted during therapy.
- Rasuvo is a pre-filled autoinjector, which can improve patient adherence and reduce injection site reactions compared to traditional syringes for some patients.
Alternative Therapies
- Other conventional synthetic DMARDs (csDMARDs) for RA/PsO/PsA: Hydroxychloroquine, Sulfasalazine, Leflunomide.
- Biologic DMARDs (bDMARDs) for RA/PsO/PsA: TNF inhibitors (e.g., adalimumab, etanercept, infliximab), IL-17 inhibitors (e.g., secukinumab, ixekizumab), IL-12/23 inhibitors (e.g., ustekinumab), T-cell costimulation modulators (e.g., abatacept), B-cell depleting agents (e.g., rituximab), JAK inhibitors (e.g., tofacitinib, baricitinib, upadacitinib).
- Other immunosuppressants (e.g., azathioprine, cyclosporine) for severe cases or specific indications.
Cost & Coverage
Average Cost:
Varies significantly by pharmacy and insurance plan. For Rasuvo 12.5mg/0.25ml, a single pen can range from $500-$1000+. per 4 pens
Generic Available:
Yes
Insurance Coverage:
Specialty Tier / Tier 4 (requires prior authorization, step therapy)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.